INVESTIGADORES
ZWIRNER Norberto Walter
congresos y reuniones científicas
Título:
CD11b+Ly6G+Ly6Cint myeloid-derived suppressor cells become expanded by medroxiprogesterone acetate in mammary tumor bearing hosts and suppress NK cell effector functions
Autor/es:
SPALLANZANI, RAÚL GERMÁN; DALOTTO-MORENO, TOMÁS; ROSSI, LUCAS EZEQUIEL; ÁVILA, DAMIÁN EZEQUIEL; ZIBLAT, ANDREA; DOMAICA, CAROLINA INÉS; FUERTES, MERCEDES BEATRIZ; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; RABINOVICH, GABRIEL ADRIÁN; SALATINO, MARIANA; ZWIRNER, NORBERTO WALTER
Lugar:
Milán
Reunión:
Congreso; 15th International Congress of Immunology; 2013
Institución organizadora:
International Union of Immunological Societies
Resumen:
The
progesterone analogue medroxyprogesterone acetate (MPA) is being widely used in
postmenopausal women, for the treatment of endometrial conditions, and as a
contraceptive. However, hormone replacement therapy in postmenopausal women has
been associated with increased incidence of breast cancer through ill-defined
mechanisms. In this work, we explored whether prolonged exposure to MPA
restrains immunosurveillance to tumors through mechanisms involving myeloid-derived
suppressor cells (MDSCs; CD11b+Gr1+, composed by CD11b+Ly6G+Ly6Cint
and CD11b+Ly6G-Ly6Chigh) and NK cells in
mammary tumor-bearing mice. Using the highly metastatic 4T1 breast tumor (which
does not express the classical progesterone receptor), we observed that MPA did
not affect primary tumor growth but promoted lung metastasis burden. This
effect was accompanied by a preferential expansion of spleen and bone marrow CD11b+Ly6G+Ly6Cint
but not CD11b+Ly6G-Ly6Chigh cells. Also, MPA
significantly increased the percentage of spleen and lung NK cells in
tumor-bearing mice with similar lung infiltration of CD11b+Gr1+
cells as compared to untreated tumor-bearing mice. However, sorted CD11b+Gr1+
cells (comprising more than 90% of CD11b+Ly6G+Ly6Cint
cells) from MPA-treated tumor bearing mice displayed a more pronounced
suppressive activity on NK cell degranulation in response to YAC-1 cells and a
stronger inhibition of IFN-g
production of NK cells in response to cytokines than those CD11b+Gr1+
cells isolated from untreated tumor-bearing mice. Thus, in breast
cancer-bearing hosts MPA promotes the accumulation of CD11b+Ly6G+Ly6Cint
cells which display a suppressive activity on NK-cell effector functions,
potentially contributing to tumor progression and metastasis.